The objective of this proposal is to develop a quantitative ultrasound technique (acoustic radiation force impulse) to noninvasively and objectively assess cervical stiffness/softness. A key benefit of our work is that development of a method to measure cervical stiffness/softness alone could have significant impact;cervical softness is a critical, yet subjective, measure made daily in an obstetrics clinic. Our goal is to use such a tool to build a comprehensive understanding of cervical microstructure and how it changes throughout normal and abnormal pregnancy. We anticipate that an enhanced understanding of cervical microstructural changes will lead to targeted investigation of specific remodeling processes in pregnancy that will promote understanding of cervical insufficiency. This in turn could guide the exploration of novel therapeutic strategies. PUBLIC HEALTH RELEVANCE: This is a proposal to develop quantitative ultrasound technology using acoustic radiation force impulse (ARFI) tools in ex vivo hysterectomy specimens in order to ultimately image and objectively quantify in vivo cervical softening in pregnancy. Cervical softening occurs throughout normal pregnancy but morbidity may occur when the cervix is too soft too early (preterm delivery) or too firm too late (postterm delivery). Currently, we have only subjective assessment of this important parameter. That alone makes objective quantification of cervical softening clinically useful. Even more, cervical softening is related to cervical microstructural arrangement and thus strength. The proposed effort involves (a) determining the sensitivity of ultrasound to the changes in stiffness/softness of the human cervix, (b) testing ARFI in isotropic and anisotropic phantoms as well as ex vivo cervical tissue in order to establish parameters for transition to in vivo cervical scanning, and (c) confirming through second harmonic generation microscopy the cervical microstructural changes that are associated with our ultrasound measurements. Besides providing an objective measure of a clinically useful parameter, development of a tool to quantify cervical softening should also give insight into cervical structure and function, including the dysfunction that leads to preterm delivery.